tbuckley/cabot-search huggingface dataset:
Development of a multiphase patient-reported outcomes dashboard to support population health and drive quality improvement in ambulatory oncology.
Authors: Sunyi Zhang, Michael Manni, Sarah Whittaker, Paige Barwick, Brian Finn, Mary Schindler, Gabe Verzino, Niren Sirohi, Jason Johnson, Ellana K Haakenstad, Hakim Lakhani, Michael J. Hassett, Nadine Jackson McCleary
Journal: Journal of Clinical Oncology (2023)

e18864 Background: The Patient Reported Data (PRD) Program at Dana-Farber Cancer Institute (DFCI) has implemented a portfolio of electronic questionnaires including patient-reported outcome measures (PROMs) and risk screeners in routine practice. Over 141,906 questionnaires have been completed by over 60,158 patients across solid tumor, liquid tumor, and supportive care (see table). We are now prepared to share this data internally in an accessible and actionable format via the development of an Outcomes Dashboard. Methods: PRD and the DFCI Clinical Operations &amp; Business Analytics team created a roadmap for iterative dashboards to be developed with Tableau 2022.1, a business analytics platform. The development team included a business analyst, data scientist, and content experts. The goal of our roadmap was to balance rapid delivery of data with the resources needed to develop more complex dashboards incorporating PRD with other data. The Outcomes Dashboard roadmap consists of four phases. Phase 1 focuses on creating a core dashboard and displaying aggregate PROMs-derived scores and risk scores with filters and stratification by patient demographics and clinical encounter data. Phase 2 adds clinical outcomes data including hospitalizations and treatment adherence. Phase 3 adds non-scored questionnaire data such as social determinants of health. Phase 4 incorporates oncology treatment data including treatment route, goals, class, and other characteristics. Results: Data was generated using Microsoft SQL Server Management Studio and loaded into Tableau to create visualizations with data refreshed daily. Dashboard Phase 1 is complete and will be released in spring 2023. Dashboard users will include executive leaders, operations, clinicians, and others. The dashboard will be used to identify differences and disparities in care delivery and outcomes by disease type, treatment, and other characteristics; highlight opportunities for interventions to improve quality and care delivery; identify areas for future research; and help fulfill emerging regulatory requirements. Conclusions: By making aggregate PRD and associated outcomes available in an accessible format, we aim to drive quality improvement and enable population health management. Future efforts will include educating users, assessing uptake of the dashboard, and partnering with stakeholders to develop clinical interventions to improve outcomes. [Table: see text]
Tumor immune infiltrates and overall survival in non-small cell lung cancer are associated with an unsupervised radiomic signature.
Authors: Jung Hun Oh, Harini Veeraraghavan, Aditya Apte, Allen Tannenbaum, Joseph O. Deasy
Journal: Journal of Clinical Oncology (2023)

e20525 Background: We investigated whether radiomic features derived from computed tomography (CT) scans are predictive of survival and are correlated with immune cell types in non-small cell lung cancer (NSCLC), employing a mathematical network-based approach. Methods: DICOM data of pre-treatment CT scans and associated clinical variables for 116 NSCLC patients were downloaded from The Cancer Imaging Atlas (TCIA). RNA-Seq gene expression profiles for the matched cases were downloaded from the GEO database (GSE103584). CIBERSORT scores that consist of 22 immune cell types were generated using the R library (CIBERSORT) on the RNA-Seq gene expression profiles. From contoured tumors on CT scans, 83 radiomic features including tumor volume were extracted, utilizing the CERR radiomics toolbox. Radiomic networks were constructed with a threshold of Spearman correlation coefficient of 0.85 between each pair of radiomic features. The mathematical network-based k-means clustering method was applied to the largest connected network component that consists of 40 radiomic features, using the Wasserstein distance from optimal mass transport (OMT), to minimize the summed distance between k partitioned centroids and their respective data points. For the sub-groups identified, Kaplan-Meier survival analysis was conducted with log-rank test and CIBERSORT scores and clinical variables were then compared among the sub-groups using Kruskal-Wallis test. Results: The median age was 69 years (range: 46–85 years). Eighty-seven patients (75.0%) were males. Most patients were former (N = 75, 64.7%) or current smokers (N = 24, 20.7%). The median follow-up time (last follow-up or death) was 44 months and 75 patients were alive at last contact. The Wasserstein distance-based k-means method resulted in 3 sub-groups (high: N = 32, medium: N = 45, low-risk: N = 39). Kaplan-Meier analysis on the 3 sub-groups showed a significant difference in overall survival with log-rank p = 0.02. There were no significant differences for the variables mentioned above among the sub-groups. Two immune cell types showed statistically significant differences among the sub-groups: mast cells resting with p = 0.004 and M2 macrophages with p = 0.013 using Kruskal-Wallis test. The values for both immune cell types increased from high &lt; medium &lt; low-risk group. There was a significant volume difference with p &lt; 0.001, but the difference did not fully account for the survival difference; the median volume was 30.8 cc, 2.7 cc, and 12.8 cc for high, medium, and low-risk groups, respectively. Conclusions: A radiomic network analysis, utilizing a mathematical network-based method, resulted in sub-groups with the survival difference in NSCLC patients. Furthermore, these sub-groups had significantly different immune cell types likely associated with the survival.
Racial disparity in cancer clinical trials: An analysis of clinicaltrials.gov protocols for race-related language and description.
Authors: Gayathri Raghupathy, Haley Bowers, Roshan Seth
Journal: Journal of Clinical Oncology (2023)

e18545 Background: Despite high cancer mortality rates in Black and Hispanic patients, they remain underrepresented in clinical trials. We analyze clinicaltrials.gov trial protocols to understand how sponsors discuss race, ethnicity, or diversity-related keywords, and map the distribution of cancer trials in the USA in relation to cancer incidence rates among Black and Hispanic Americans. Our study highlights the potential of enhanced sponsor information and data-driven site selection to reduce racial disparities in clinical trials. Methods: The US oncology trials from NIH’s clinicaltrials.gov were searched for racial disparity-related keywords using Kognitic© NLP algorithms. Keywords such as "racial," "ethnicity," "minority," "African American,”, "Hispanic” etc. were included. Only Hispanic and African American races were considered. Data were verified, classified based on keywords found. Zip codes of recruiting clinical trial sites were mapped to high-cancer-incidence counties among Hispanics and Black Americans (sources: statecancerprofiles.cancer.gov and unitedstateszipcodes.org). Results: We found 8338 (21% of all US cancer trials) clinical trials addressing racial disparity in cancer, with 4.3% being industry-sponsored, 8.3% academic-industry collaborations, and 87.3% non-industry-sponsored. 50% of the trials were interventional and the other 50% were observational, with biopharma as the primary industry represented. In industry-sponsored trials, only 10.3% directly explore race-based outcome differences, with the remainder collecting demographic data or having patients self-report their race. After comparing the locations of cancer clinical trials currently underway in the United States to counties with the highest cancer incidence rates among Black and Hispanic Americans, we discovered that only a limited number of clinical trial sites are in those high-incidence counties. Only four out of the top ten counties with the highest cancer incidence rates for Blacks and one out of the top ten for Hispanics have clinical trials actively recruiting patients, with most trials in both populations being conducted by non-industry sponsors. Conclusions: Our findings indicate that a limited number of cancer clinical trials mention race and ethnicity in publicly available trial protocols, and even fewer industry trials include race-related information. Our site analysis shows that a major gap in access to trials in areas with high cancer incidence rates, particularly for populations with low socioeconomic status. More analysis is needed to understand the relationship between trials and demographic conditions in America. Providing details on plans to address racial disparities in recruitment, trial design, and site selection will promote inclusive trial design that are accurate assessment of how drugs work in various types of patients.
Age-standardized incidence, mortality rates, mortality-to-incidence ratios, and disability-adjusted life years for acute lymphoblastic leukemia in the European Union 15 + countries, Australia, and United States of America.
Authors: Akhil Jain, Chinmay Jani, Sagar Patel, Maharshi Raval, Harpreet Singh
Journal: Journal of Clinical Oncology (2023)

e19052 Background: Though acute lymphoblastic leukemia (ALL) has been described historically more frequently in children, its burden has been increasing in adults. Therefore we aimed to describe ALL's age-standardized rates in incidence (ASIR), mortality (ASMR), and disability-adjusted life years (DALYs) between 1990-2019 between countries with comparable healthcare structure. Methods: Using the International Classification of Diseases versions 10 and 9, we extracted data from the Global Burden of Disease Study database for European Union (EU 15+) countries, Australia and USA. Individual countries' ASIR, ASMR, and DALYs stratified by sex were extracted for 1990-2019, and mortality-to-incidence indices (MII) were calculated. The indices were reported per 100,000 people. Results: ASIRs increased globally (males +60.35%, females +57.02%) as well as in all countries, with the highest in Portugal for males (+315.4%) and females (+195.06%). ASIR increase was less than global aggregate figures in Australia and Norway. USA had decreasing ASIR for males (-19%) and minimal change in females (+1%). ASMR decreased globally (males -15.75%, females -21.45%), all countries had decreasing ASMR across males and females with the highest decrease for males in Denmark (-56.28%) and females in Portugal (-56.16%). More importantly, MII had decreased globally, reaching 50% change both in males and females. USA observed lesser decrease in MII for males (-11%) and females (-24%) whereas all other EU countries and Australia had larger changes ( &gt; 50%). Though Italy had the highest ASIR (males 11.54, females 8.33) as well as ASMR (males 0.71, females 0.46) in 2019, its MII had large changes (males -70%, females -54%). DALYs decreased in males (-20.23%) and females (-26.86%) globally. Decrease in Australia was more pronounced in Australia (males -50%, females -47%) than USA (males -36%, females -30%) and many other EU countries. Greece had smallest decrease in DALYs (males -16.04%) and Austria (females -16.92%). Conclusions: Though the incidence is increasing, mortality of ALL is decreasing globally for males and females. MII and DALYs have also decreased for males and females despite increased ASIR. This reflects the success on multiple fronts including precise diagnosis and prognostication, and the utility of dose-intensive chemotherapy, which can achieve sustainable complete remission. Implementing monoclonal antibodies in first-line treatment over the next few years will improve disease control.
STAR-121: A phase 3, randomized study of domvanalimab (DOM) and zimberelimab (ZIM) in combination with chemotherapy vs pembrolizumab (pembro) and chemotherapy in patients with untreated metastatic non-small cell lung cancer (mNSCLC) with no actionable gene alterations.
Authors: Delvys Rodriguez-Abreu, Jhanelle Elaine Gray, Myung-Ju Ahn, Melissa Lynne Johnson, Xinwei Yu, Xueying Chen, Patrick Hoang Phuong, Jongseok Kim, Martin Reck
Journal: Journal of Clinical Oncology (2023)

TPS9141 Background: Although immune checkpoint inhibitors have improved clinical outcomes in mNSCLC, the majority of patients will experience progression and shorter survival. Thus, an urgent need exists for more effective treatment options in mNSCLC. DOM is an anti-TIGIT IgG1, Fc-silent monoclonal antibody designed to inhibit the interaction between TIGIT and its ligand, CD155, thereby reducing immunosuppression of T cells and natural killer cells and promoting antitumor activity. ZIM is an anti–PD-1 IgG4 monoclonal antibody with demonstrated antitumor activity in vivo and preliminary clinical activity in multiple tumor types. Preliminary studies have shown that dual blockade of TIGIT and PD-(L)1 increases antitumor activity relative to PD-(L)1 inhibition. In ARC-7, a randomized phase 2 study in PD-L1–high, first-line NSCLC, DOM and ZIM in combination recently demonstrated a higher objective response rate (ORR) and longer median progression-free survival (PFS) than ZIM monotherapy. We hypothesize that DOM and ZIM in combination with chemotherapy will improve clinical outcomes in patients with untreated mNSCLC without EGFR or ALK aberrations regardless of PD-L1 expression. Methods: STAR-121 is a phase 3, global, open-label, randomized study to evaluate the safety and efficacy of DOM and ZIM plus chemotherapy vs pembro plus chemotherapy as first-line therapy for patients with mNSCLC with no EGFR or ALK aberrations or other known actionable gene alterations. Approximately 720 patients will be randomized into 3 groups (A, B, or C) in a 4:4:1 ratio and stratified by baseline PD-L1 tumor proportion score ( &lt; 50% vs ≥50%), histology (squamous vs nonsquamous), and geographic region (East Asia vs non–East Asia). Eligible patients are aged ≥18 with untreated mNSCLC with no EGFR or ALK aberrations. Group A will receive DOM 1200 mg + ZIM 360 mg + platinum-doublet chemotherapy (PT), group B will receive pembro 200 mg + PT, and group C will receive ZIM 360 mg + PT. DOM, ZIM, and pembro will be administered until disease progression (PD) as assessed by blinded independent central review (BICR) per RECIST 1.1 or intolerable toxicity or for up to 35 doses. Study treatment will be administered IV every 3 weeks. PT will be chosen by investigators based on tumor histology and administered for the first 4 cycles, after which, pemetrexed can be continued for patients with nonsquamous histology until PD or intolerable toxicities. The primary endpoints are PFS by BICR and overall survival. Key secondary endpoints are ORR and duration of response by BICR, safety, and quality of life. This study is currently enrolling globally. Clinical trial information: NCT05502237 .
Safety of concurrent use of radiotherapy for second primary malignancy (SPM) in patients with chronic lymphocytic leukemia (CLL) receiving novel agent therapy.
Authors: Samuel R Kosydar, Sameer Ashok Parikh, Scott Lester, Kari G. Rabe, Wei Ding, Saad Kenderian, Yucai Wang, Eli Muchtar, Amber Koehler, Susan M. Schwager, Susan L. Slager, Neil E. Kay, Timothy Call, Will Breen, Paul Joseph Hampel
Journal: Journal of Clinical Oncology (2023)

e19507 Background: Patients (pts) with CLL are at elevated risk of developing non-hematologic malignancies. Radiation therapy (RT) is a critical component of management in localized solid organ malignancies. Novel agents (NA) are widely used in CLL treatment; however, safety data are lacking to guide treatment of pts requiring concurrent RT and NA. Methods: We identified pts treated concurrently with NA for CLL and RT for second primary malignancy (SPM) at Mayo Clinic from 2014-2022. Adverse events within 3 months of RT were evaluated using the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for hematological toxicity and the Common Terminology Criteria for Adverse Events (CTCAE) version 5 for non-hematological toxicity. Patients without seamless, concurrent treatment with NA and RT were excluded. Results: Twenty-six pts were included. NA therapy consisted of ibrutinib (n = 23), acalabrutinib (n = 2), and venetoclax (n = 1). Median follow up time since RT completion was 1.5 years. The median age at NA initiation was 67 years (range:46-85) and at RT start was 68 years (range: 51-85); 92% of pts were male. NA was first treatment in 23% of pts; the median number of prior lines of therapy was 1 (range: 0-4). IGHV was unmutated in 82% and TP53 aberration was present in 24% of evaluable patients. SPM sites included prostate (n = 9), head/neck (n = 8), lung (n = 3), and brain, breast, bone, skin, kidney, and thymus (n = 1 each). The most common conventionally fractionated prescriptions (cGy/fx) were 6000/30 (n = 6) and &gt; 6000-7020/20-33 (n = 7). SBRT ranged from 3300/5 to 5400/3 (n = 8). Five pts received other, varied RT prescriptions. Overall, 3 (12%) pts experienced at least one grade 3/4 toxicity. Grade 3/4 thrombocytopenia was observed in 2 (8%) pts and grade 3/4 neutropenia was observed in 2 pts per iwCLL criteria. Grade ≥3 non-hematological toxicities occurred in two pts that required hospitalization for critical illness, including 1 pt with grade 5 respiratory failure within 6 weeks after RT. Dose de-escalation of ibrutinib was reported in one case for pancytopenia attributed to use of a radiosensitizing agent. There were no cases of RT dose modification. Conclusions: Continuing NA CLL therapy during RT did not result in unexpected toxicities. This approach may maintain CLL disease control without compromising management of the SPM. [Table: see text]
Connecting Black families in Houston, Texas, to hereditary cancer genetic counseling, genetic testing, and cascade testing by using a simple cancer genetic risk assessment and telegenetics.
Authors: Darya Aleksandrovna Kizub, Sreejesh Shanker, Sierra Green, Autumn Vara, Banu Arun
Journal: Journal of Clinical Oncology (2023)

TPS10638 Background: Hereditary breast and colorectal cancers accounts for 5-10% of all cases, but less than half of all eligible patients undergo NCCN guideline-concordant screening. This proportion is even lower among Black patients, who have a higher breast cancer and colorectal incidence and mortality. Recruitment through community organizations has been shown to identify patients who are eligible for genetic testing but have not been offered it by their doctor. Our one-page cancer genetic risk assessment (CGRA) and telegenetics were previously shown to improve adherence to genetic testing guidelines for hereditary breast and ovarian cancer. Our objective is to identify adults eligible for hereditary breast and colorectal cancer syndromes genetic testing using trusted community organizations that serve the Black community as entry points, reach them with our tailored program, and measure impact. Methods: In this prospective single-arm trial, adults of &gt; 18 years old who self-identify as Black or African American are recruited during events put together by community organizations in Houston, Texas. The CGRA was modified to encompass hereditary breast and colorectal cancer syndromes based on NCCN guidelines. To improve convenience, eligible participants can be consented and fill out the CGRA in-person or via QR code link using a smart phone. Study team members attend community events and are also available via phone to help with informed consent, CGRA, etc. Those at high risk for hereditary breast and colorectal cancer syndromes are provided with educational materials and can be sent the saliva-based kit or complete it on-site. When results of genetic testing include a pathogenic mutation (PV) or variant of uncertain significance, individuals receive telegenetic counseling and risk reduction resources, including about cascade genetic testing. Others are notified of negative results. The program includes education for interested community organization members about importance of genetic testing. The program is projected to reach 1,000 participants with 300 completing genetic testing and identification of 11 PV. The study is overseen by a Community Advisory Board. Impact will be evaluated via a multiple methods design using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) Qualitative Evaluation for Systematic Translation (QuEST) framework six months after program start. Quantitative data will be analyzed using descriptive statistics and standard tests of association. Data collected via semi-structured interviews with participants and program implementers will be audio-recorded, transcribed, double-coded, and analyzed via thematic analysis. Enrollment started December of 2022. 15 participants patients enrolled during two community events. Clinical trial information: NCT05694559 .
Ibrutinib dose modifications for management of cardiac adverse events in patients with B-cell malignancies: Pooled analysis of 10 clinical trials.
Authors: Deborah Marie Stephens, Jennifer R. Brown, Shuo Ma, Michael Wang, Carolina D. Moreno, Tadeusz Robak, Don A. Stevens, Xin (Shane) Li (Lee), Chadi Saifan, Emily Hsu, Sima Patel, Jan Andreas Burger
Journal: Journal of Clinical Oncology (2023)

7538 Background: Continuous therapy with once-daily ibrutinib (Ibr) is associated with long-term PFS in pts with B-cell malignancies. Dose reduction is a potential AE management approach that may optimize treatment outcomes. We evaluated outcomes with dose reductions in Ibr-treated pts with cardiac AEs. Methods: Data were pooled for Ibr-treated pts from 10 studies of CLL (n=781), mantle cell lymphoma (MCL; n=250), marginal zone lymphoma (MZL; n=63) or Waldenström macroglobulinemia (WM; n=169). Cardiac AEs, initial and recurrent, were identified by preferred terms within the cardiac disorders system organ class. Recurrence was defined as an AE of same or worse grade, and was measured up to 30 days after last dose of ibrutinib or start of next-line therapy, whichever occurred earlier. Results: Overall, 234/1263 pts (19%) had cardiac AEs of any grade. Twelve pts were excluded from the analysis: 9 who had a dose reduction prior to a cardiac AE (0.7%) and 3 who had a fatal cardiac AE with no prior cardiac AE (0.2%). Of the remaining 222 pts with grade 1-4 cardiac AEs, 22 (10%) had Ibr dose reduction to 420 mg (n=3), 280 mg (n=10), or 140 mg (n=9) after a cardiac AE. These pts (n=22) tended to be older (≥75 y: 45% vs 29%), less heavily pretreated (≥1 prior therapy: 45% vs 73%), and with a lower Ibr discontinuation rate (23% vs 48%) than those without dose reduction (n=200). Recurrence of the same cardiac AEs at the same or worse severity was less frequent in pts with dose reductions, both overall (14% vs 18%) and as serious AEs (5% vs 10%). No pt died due to cardiac AE recurrence. Among pts with cardiac AEs who started with the 420 mg Ibr dose (177/222; excludes 45 patients with MCL or MZL who per label start with 560 mg dose), no cardiac AE recurred at same or worse severity in the subset with dose reductions (Table). PFS was not negatively impacted by dose reduction, both overall (n=22; median PFS not reached [NR], 24-mo PFS: 91%), and in those who started with the 420 mg dose (n=18; median PFS NR; 24-mo PFS, 94%). Conclusions: Dose reduction for cardiac AEs may enable pts to continue to benefit from long-term Ibr and mitigate the risk of cardiac AE recurrence or worsening. Clinical trial information: NCT01105247 , NCT01236391 , NCT01578707 , NCT01722487 , NCT01611090 . [Table: see text]